Thalidomide and the immune system 3. simultaneous up- and down-regulation of different integrin receptors on human white blood cells

Nogueira, Ana Cláudia Fernandes; Neubert, Reinhard; Helge, H; Neubert, Diether

doi:10.1016/0024-3205(94)90099-x

Cited by 86 publications

(43 citation statements)

References 19 publications

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“…Thd treatment did not affect the surface expression of CD11a by neutrophils in our studies, which was consistent with the in vitro effect of Thd (Geitz et al, 1996). However, the expression of CD62L by neutrophils was not affected by Thd treatment in our studies, which was in contrast to the report that Thd downregulated the surface expression of L-Selectin by neutrophils (Nogueira et al, 1994;Geitz et al, 1996). The reason for this discrepancy is not clear, but it may be related to treatment duration, species difference and neutrophil location.…”

Section: Discussionsupporting

confidence: 89%

“…There is evidence that Thd modulates the surface expression of adhesion molecules by neutrophils (Nogueira et al, 1994). Therefore, we evaluated the effect of Thd on the surface expression of CD18, CD62L, CD11a and CD44 by neutrophils in Thd-treated mice.…”

Section: Neutrophils In the 14-day Thd-treated Mice Were Different Frmentioning

confidence: 98%

“…Although it was hypothesized that an increased granulopoiesis might be involved (Invernizzi et al, 2005), the exact mechanism that Thd treatment increased neutrophils in these organs was not clear. There is evidence that Thd downregulates the expression of surface adhesion molecules such as L-Selectin (CD62L) by neutrophils (Nogueira et al, 1994;Geitz et al, 1996). An increased infiltration of neutrophils in the liver after L. monocytogenes infection was also observed in LFA-1 (CD11a/CD18)-deficient mice (Miyamoto et al, 2003).…”

Section: Introductionmentioning

confidence: 98%

“…Thalidomide [N(α)-phthalimidoglutarimide; Thd] has been identified as an effective immunomodulatory drug with therapeutic potentials for a variety of diseases including multiple myeloma and myelodysplastic syndromes (MDS) despite its toxic potencies (Nogueira et al, 1994;Davies et al, 2001). Patients with MDS often develop neutropenia and are associated with a high mortality rate due to recurrent bacterial infections (Mufti et al, 1985;Kouides and Bennett, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Auttachoat¹,

Zheng²,

P.³

et al. 2007

Toxicology and Applied Pharmacology

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Previously, we have reported that thalidomide (Thd) can enhance neutrophil function in female B6C3F1 mice. The present study was intended to evaluate the mechanisms underlying the enhanced neutrophil responses following Thd treatment intraperitoneally (100 mg/kg) for 14 or 28 days. Treatment with Thd increased the numbers of neutrophils in the spleen, peripheral blood, bone marrow, peritoneal cavity and lung of female B6C3F1 mice when compared to the vehicle control mice. Thd treatment for 14 days increased the percentages and the number of neutrophils in the spleen in the first eight hours (peaking at 2 h) after the last Thd treatment, and it returned to the baseline after 24 h. However, Thd treatment for 28 days increased the percentages and number of neutrophils in the spleen even at the 24-h time point after the last Thd treatment. These neutrophils were demonstrated to be functional by the myeloperoxidase activity assay. Further studies have ruled out the possibility of an increased bone marrow granulopoiesis following Thd treatment. Flow cytometric analysis of the surface expression of adhesion molecules suggested that Thd treatment for either 14 or 28 days decreased the surface expression of either CD18 or CD44 by bone marrow neutrophils. On the other hand, the surface expression of both CD18 and CD44 by splenic neutrophils was increased following Thd treatment for 28 days but not for 14 days. No effect was produced for other cell surface molecules such as CD62L and CD11a. It was possible that decreased surface expressions of CD18 and CD44 facilitated neutrophils' release from the bone marrow; increased surface expressions of CD44 and CD18 by splenic neutrophils after 28 days of Thd treatment increased their ability to remain in the periphery. Taken together, Thd treatment increased neutrophils in female B6C3F1 mice, at least partially, through differentially modulating the surface expression of CD18 and CD44 by the neutrophils in the bone marrow and spleen.

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Section: Discussionsupporting

confidence: 89%

Section: Neutrophils In the 14-day Thd-treated Mice Were Different Frmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Auttachoat¹,

Zheng²,

P.³

et al. 2007

Toxicology and Applied Pharmacology

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“…Thalidomide modulates adhesive Leukemia interactions 22 and induces changes in the expression level of surface molecules.…”

Section: Discussionmentioning

confidence: 99%

Thalidomide for the treatment of patients with myelodysplastic syndromes

et al. 2002

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We examined the efficacy of thalidomide in 34 patients with myelodysplastic syndromes (MDS): five RAEB-T, four RAEB, three CMML, six RARS, and 16 RA. Patients belonged to the following cytogenetic groups: 15 complex abnormal karyotypes, 12 normal karyotypes, four cases with 5q− as sole anomaly and three single aberrations. The median thalidomide dose was 400 mg/day (25/34 patients). Four patients discontinued the study after less than 5 weeks, because of fatigue (three) or skin rash (one). One patient died of heart failure after 4 weeks. In the remaining 29 patients (median follow-up: 13 months), treatment responses were classified according to the IWG criteria. Six patients (four RA, two CMML) showed progressive disease (five with transformation into AML) and four patients showed stable disease. Hematological improvement (HI) was observed in 19 patients. Nine of the responders (three RA, one RARS, two RAEB, three RAEB-T) achieved partial remission with granulocytes у1500/ l, Hb Ͼ 11 g/dl and platelets у100 000/ l. Four patients (one RARS, one CMML, one RAEB, one RAEB-T) had a major response, with platelet and RBC transfusion independence. Six patients (five RA, one RARS) showed minor responses (three HI-E, two HI-E+HI-P, one HI-E+HI-N). Hematological improvement occurred after a median of 2 months of thalidomide treatment. Two patients (RAEB-T) relapsed after a partial remission lasting 8 and 16 months, respectively. In summary, a therapeutic benefit was achieved in 19 of 34 study patients (56%).

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Pharmacology and the Use of Immunosuppressive Agents After Hematopoietic Cell Transplantation

Chao¹

2003

Thomas' Hematopoietic Cell Transplantation

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Thalidomide and the immune system 3. simultaneous up- and down-regulation of different integrin receptors on human white blood cells

Cited by 86 publications

References 19 publications

Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Differential surface expression of CD18 and CD44 by neutrophils in bone marrow and spleen contributed to the neutrophilia in thalidomide-treated female B6C3F1 mice

Thalidomide for the treatment of patients with myelodysplastic syndromes

Pharmacology and the Use of Immunosuppressive Agents After Hematopoietic Cell Transplantation

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